EP1.03-08 MiR-744 Facilitates Non-Small Cell Lung Cancer Progression by Transcriptional Regulation of c-FOS

Abstract

Metastasis is the leading cause of lung cancer associated death. Here, we focused on the function and downstream molecular mechanism of miR-744 and its potential clinical application in non-small cell lung cancer (NSCLC) progression. The clinical cohort and data from TCGA were analyzed for the correlation of miR-744 and clinical outcomes. Multiple NSCLC cell lines and a NSCLC xenograft model were applied for the functional studies in vitro and in vivo respectively. Reporter assays were used for transcriptional regulatory mechanism study. It was confirmed that the overexpression of miR-744 was significantly correlated with lymph node metastasis and poor prognosis in NSCLC. It was an independent prognostic molecular marker for NSCLC. Both in vitro and in vivo studies revealed that miR-744 overexpression aggravated the invasion and metastasis of NSCLC cells. MiR-744 positively regulated c-FOS by directly binding to the promoter of c-FOS. We also identified -358 to -332 bp and -221 to -192 bp upstream of c-FOS gene as the direct and efficient miR-744 binding site in c-FOS promoter region. MicroRNA-744 could regulate MAPK signaling and enhanced the resistance of lung cancer cells to radiotherapy and paclitaxel. Our findings uncover the function of miR-744 in NSCLC and reveal a novel mechanism of miR-744 in mediating growth and metastasis of NSCLC cells. Our data suggests that miR-744 may serve as a possible therapeutic target for NSCLC. Support: 81572279, 2016J004, LC2016PY016, 2018CR033.